The first objective of this project is to develop analytical procedures for the measurement of nanomole and picomole quantities of diethylstilbestrol in tissues and body fluids utilizing deuterated diethylstilbestrol and an isotope dilution technique that depends upon the measurement in the gas chromatograph-mass spectrometer of the relative abundance of ions derived from the deuterated and undeuterated compounds. We wish to extend this technique to studies of the metabolism of diethylstilbestrol by placental and fetal tissues derived from humans and from laboratory mammals. In the metabolic experiments we will employ a double isotope technique (H2 and C14) to detect, characterize and measure any transformation products. These experiments are designed to provide some answers to the many questions that are raised by the carcinogenic action of diethylstilbestrol administered to pregnant women that is expressed as adenocarcinoma of the vagina in their teen-aged daughters. The project outlined should help to determine if the carcinogenic agent is diethylstilbestrol itself, or if a metabolite is formed in the placenta or in a fetal tissue that may be the carcinogenic agent.